Drug-Resistance Biomarkers in Patient-Derived Colorectal Cancer Organoid and Fibroblast Co-Culture System

Colorectal cancer, the third most commonly occurring tumor worldwide, poses challenges owing to its high mortality rate and persistent drug resistance in metastatic cases. We investigated the tumor microenvironment, emphasizing the role of cancer-associated fibroblasts in the progression and chemoresistance of colorectal cancer. We used an indirect co-culture system comprising colorectal cancer organoids and cancer-associated fibroblasts to simulate the tumor microenvironment. Immunofluorescence staining validated the characteristics of both organoids and fibroblasts, showing high expression of epithelial cell markers (EPCAM), colon cancer markers (CK20), proliferation markers (KI67), and fibroblast markers (VIM, SMA). Transcriptome profiling was conducted after treatment with anticancer drugs, such as 5-fluorouracil and oxaliplatin, to identify chemoresistance-related genes. Changes in gene expression in the co-cultured colorectal cancer organoids following anticancer drug treatment, compared to monocultured organoids, particularly in pathways related to interferon-alpha/beta signaling and major histocompatibility complex class II protein complex assembly, were identified. These two gene groups potentially mediate drug resistance associated with JAK/STAT signaling. The interaction between colorectal cancer organoids and fibroblasts crucially modulates the expression of genes related to drug resistance. These findings suggest that the interaction between colorectal cancer organoids and fibroblasts significantly influences gene expression related to drug resistance, highlighting potential biomarkers and therapeutic targets for overcoming chemoresistance. Enhanced understanding of the interactions between cancer cells and their microenvironment can lead to advancements in personalized medical research.

New Monocyclic Terpenoid Lactones from a Brown Algae Sargassum macrocarpum as Monoamine Oxidase Inhibitors

Algae are unique natural products that can produce various types of biologically active compounds. The 70% ethanol extract of brown algae Sargassum macrocarpum collected from the East Sea of Korea inhibited human monoamine oxidases A and B enzymes (hMAO-A and hMAO-B) at a 50 μg/mL concentration. The bioassay-guided isolation was performed through solid-phase extraction and the Sepbox system followed by serial high-performance liquid chromatography on the reverse phase condition, resulting in the identification of two new monocyclic terpenoid lactones, sargassumins A and B (1 and 2). The planar structures of the compounds were determined by a combination of spectroscopic data. The absolute configurations were determined by the interpretation of circular dichroism data. Compound 1 exhibited mild hMAO-A inhibition (42.18 ± 2.68% at 200 μM) and docked computationally into the active site of hMAO-A (−8.48 kcal/mol). Although compound 2 could not be tested due to insufficient quantity, it docked better into hMAO-A (−9.72 kcal/mol). Therefore, the above results suggest that this type of monocyclic terpenoid lactone could be one of the potential lead compounds for the treatment of psychiatric or neurological diseases

Novel Diagnostic Biomarkers for High-Grade Serous Ovarian Cancer Uncovered by Data-Independent Acquisition Mass Spectrometry

High-grade serous ovarian cancer (HGSOC) represents the major histological type of ovarian cancer, and the lack of effective screening tools and early detection methods significantly contributes to the poor prognosis of HGSOC. Currently, there are no reliable diagnostic biomarkers for HGSOC. In this study, we performed liquid chromatography data-independent acquisition tandem mass spectrometry (MS) on depleted serum samples from 26 HGSOC cases and 24 healthy controls (HCs) to discover potential HGSOC diagnostic biomarkers. A total of 1,847 proteins were identified across all samples, among which 116 proteins showed differential expressions between HGSOC patients and HCs. Network modeling showed activations of coagulation and complement cascades, platelet activation and aggregation, neutrophil extracellular trap formation, toll-like receptor 4, insulin-like growth factor, and transforming growth factor beta signaling, as well as suppression of lipoprotein assembly and Fc gamma receptor activation in HGSOC. Based on the network model, we prioritized 28 biomarker candidates and validated 18 of them using targeted MS assays in an independent cohort. Predictive modeling showed a sensitivity of 1 and a specificity of 0.91 in the validation cohort. Finally, in vitro functional assays on four potential biomarkers (FGA, VWF, ARHGDIB, and SERPINF2) suggested that they may play an important role in cancer cell proliferation and migration in HGSOC. All raw data were deposited in PRIDE (PXD033169).N

Identification of candidate variants and genes associated with temperature tolerance in olive flounders by Genome-Wide Association Study (GWAS)

The Republic of Korea is one of the largest producers of farm-raised olive flounder (Paralichthys olivaceus), accounting for nearly half of the global production. However, global warming has affected the aquaculture industry worldwide as it impacts survival, growth, and immunity and accelerates increases in pathogen load. In this study, we identified thermal stress-related genes in olive flounder using a genome-wide association study (GWAS) to provide a basis for marker-assisted selection and the development of temperature-resistant olive flounder in response to global warming. In total, 768 healthy olive flounder (weight of 159 ± 29.9 g and length of 25.42 ± 1.63 cm) were subjected to thermal stress (19.4–32.5 °C), and dead fish (537) were collected every 30 min. The fin tissues were isolated from all dead and surviving fish (231) and used for gDNA extraction. A high-quality 70 K SNP chip was used for genotyping, and 58,920 SNPs were obtained from 726 individuals after quality filtering. The GWAS identified 216 statistically significant SNPs at the Bonferroni cutoff (8.5 × 10−7). All significant SNPs were located on chromosome (chr) 18 (39 SNPs), chr 19 (176 SNPs), and contig 28 (AGQT02031776.1). After the SNP annotation, 13, 67, and 135 SNPs were identified in exons, introns, and intergenic regions, respectively. Gene and functional annotations revealed that almost all significant SNPs were directly or indirectly associated with the thermal stress response. Annotated genes were further categorized into the following functional groups: metabolic, neural and neuroendocrine, molecular and cellular, and physiological and behavioral responses. The significant SNP-harboring genes identified in this study could be used for marker-assisted genomic selection in future breeding programs